Gut microbiota is among the factors that may be involved in healthy aging. Broader and geographically spread studies on gut microbiota of centenarians can help in identifying a common signature of longevity. We identified an endogamous Indian population with high centenarian prevalence. Read More

In replicative senescence, cells with critically-short telomeres activate a DNA-damage response leading to cell-cycle arrest, while those without telomere dysfunction would be expected to cycle normally. However, population growth declines more gradually than such a simple binary switch between cycling and non-cycling states would predict. We show here that late-passage cultures of human fibroblasts are not a simple mixture of cycling and non-cycling cells. Read More

In clinical medicine, the concept of frailty is viewed as a state of high vulnerability to adverse health outcomes in people of the same age. Frailty is an important challenge because the loss of physiological reserve means that even minor stressors can lead to disability and death in those who are frail. Even so, the biology of frailty is not well understood. Read More

Tau, a microtubule-associated protein promotes assembly and stability of microtubules which is related to axoplasmic flow and critical neuronal activities upon physiological conditions. Under neurodegenerative condition such as in Alzheimer's Disease (AD), tau-microtubule binding dynamics and equilibrium are severely affected due to its aberrant post-translational modifications including acetylation and hyperphosphorylation. This event results in its conformational changes to form neurofibrillary tangles (NFT) after aggregation in the cytosol. Read More

Caloric restriction (CR) is the most effective intervention to improve health span and extend lifespan in preclinical models. This anti-aging effect of CR is related to attenuation of oxidative damage in various tissues, with divergent results in the brain. We addressed how brain oxidoreductive balance would be modulated in male Sprague-Dawley (SD) rats submitted to a 40% CR from 8 to 19 months of age, by reference to ad libitum-fed (AL) rats at 2 and 19 months of age. Read More

One hallmark of molecular aging is glycation, better known as formation of so-called advanced glycation end products (AGEs), where reactive carbonyls react with amino-groups of proteins. AGEs accumulate over time and are responsible for various age-dependent diseases and impairments. Two very potent dicarbonyls to generate AGEs are glyoxal (GO) and methylglyoxal (MGO). Read More

Introduction: The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene (APOE) variants (ε2, ε3, ε4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the ε4 variant is associated with Alzheimer's disease (AD), it might represent an opportunity for exploring the relationship of APOE with physiological and pathological aging. Read More

From a biological point of view, aging can be considered a progressive inability of an organism to react to stress, maintain homeostasis, and survive unfavourable changes during post-maturational life. The expression of several adipokines changes during aging and for some changes, a role in the onset of chronic disease and frailty has been proposed. Among adipokines, resistin was shown in recent studies to play a key role in aging. Read More

Authors:

Interactions between extracellular matrix (ECM) and fibroblasts are essential for maintaining dermis integrity, and are subject to ageing. The ötissue skeleton' network connects ECM to the nucleus and DNA, impacting nuclear shape and gene expression. In a previous Mech Ageing Dev publication, we have presented a transcriptomic study of papillary (Fp) and reticular (Fr) fibroblasts, with a main focus on Fp ageing. Read More

Klotho gene polymorphisms have been implicated in healthy aging, but inconsistences in findings from previous case-control studies have raised concerns regarding the associations between KLOTHO gene polymorphisms and susceptibility to aging-related diseases and longevity. Hence, this meta-analysis was performed. We assessed the associations between two polymorphisms (G-395 A/rs1207568 and F352 V/rs9536314) and five parameters (urolithiasis, cognitive impairment, cardiovascular disease, cancer, and longevity) by calculating pooled odds ratios with 95% confidence intervals. Read More

Cellular senescence is a phenomenon of irreversible growth arrest in mammalian somatic cells in culture. Various stresses induce cellular senescence and indeed, we have found that excess thymidine effectively induces cellular senescence in human cells. Further, many reports indicate the implication of chromatin proteins in cellular senescence. Read More

MicroRNA's are small non-coding RNAs that regulate the expression of genes by targeting the 3' UTR's of mRNA. Studies reveal that miRNAs play a pivotal role in normal musculoskeletal function such as mesenchymal stem cell differentiation, survivability and apoptosis, osteogenesis, and chondrogenesis. Changes in normal miRNA expression have been linked to a number of pathological disease processes. Read More

Circular RNA (circRNA) is a class of newly discovered noncoding RNA (ncRNA), presenting as a special covalent loop without a 5' cap or 3' tail. Multiple biological properties of circRNA have been revealed during the past decades, such as widespread expression, high conservation, cell-specificity, tissue-specificity and developmental stage-specific expression patterns, as well as resistance to RNase R digestion. CircRNA also exhibits diverse biological functions, including regulation of host genes, alternative splicing, miRNA sponges, protein traps and even protein synthesis. Read More

Authors:

University of Groningen, European Research Institute for the Biology of Aging, University Medical Center Groningen, Groningen, Netherlands. Electronic address:

Cellular senescence is a state of irreversible growth arrest characterized by hypertrophy and secretion of various bioactive molecules, a phenomenon defined the Senescence-Associated Secretory Phenotype (SASP). Senescent cells are implicated in a number of biological functions, from embryogenesis to aging. Significantly, excessive accumulation of senescent cells is associated to a decline of regenerative capacity and chronic inflammation. Read More

Authors:

Many studies show that daily consumption of high-fiber diet is associated with a reduced risk of developing kidney stones, inflammatory disease, colon cancer and other malignancies, obesity, type II diabetes, and cardiovascular disease. Dietary fibers are non-digestible polysaccharides that are composed of complex carbohydrates. Based on their relative solubility in water, dietary fibers can be divided into insoluble and soluble forms. Read More

Many insect behaviors, including foraging, aggression, mating or group behavior, are tightly regulated by pheromones. Recently, it has been shown that pheromones may influence extreme longevity in the honeybee Apis mellifera, while changes in pheromone profile have been observed during ageing in Drosophila melanogaster. These data suggest a potential link between the pheromone system, behavior and longevity in insects. Read More

While deviations from the optimal phenotype are deleterious, increased variation can prevent population extinction under severe stresses. Cell division asymmetry is an important source of microbial phenotypic heterogeneity. A consecutive set of asymmetric divisions can cause the gradual accumulation of deleterious factors and, at late stages, the death of old pole (mother) cells. Read More

Geroprotectors, a class of drugs targeting multiple deficits occurring with age, necessitate the development of new animal models to test their efficacy. The COST Action MouseAGE is a European network whose aim is to reach consensus on the translational path required for geroprotectors, interventions targeting the biology of ageing. In our previous work we identified frailty and loss of resilience as a potential target for geroprotectors. Read More

Authors:

Key discoveries in aging research have been made possible with the use of model organisms. Caenorhabditis elegans is a short-lived nematode that has become a well-established system to study aging. The practicality and powerful genetic manipulations associated with this metazoan have revolutionized our ability to understand how organisms age. Read More

Intense research during the last few years has elucidated a number of mechanisms of the complex human aging process. Among the body organs, skin has a distinguished role in aging perception both because it constitutes the organ on which the first signs of aging are mostly visible and because skin is recognized as an indicator of human health. Analogous to all other organs, skin undergoes multiple morphological and functional changes with age affected by extrinsic and intrinsic factors. Read More

In older adults, the prevalence of osteoarthritis (OA) increases directly with age and is the most common cause of chronic disability. It is necessary to recognize that OA is a degenerative disease that strongly correlates with age, and often promotes elevated levels of cartilage injury. Chondrocytes undergo an age-dependent decline in proliferative and synthetic capacity. Read More

Authors:

Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address:

Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities best described as an accelerated aging phenotype. Read More

FAHD1, a member of the FAH superfamily of enzymes, was identified in a proteomic screen for mitochondrial proteins with differential expression in young versus senescent human endothelial cells. FAHD1 acts as oxaloacetate decarboxylase, and recent observations suggest that FAHD1 plays an important role in regulating mitochondrial function. Thus, mutation of the nematode homolog, fahd-1, impairs mitochondrial function in Caenorhabditis elegans. Read More

Although the beneficial effects of calorie restriction (CR) on health and aging were first observed a century ago, the specific macronutrients and molecular processes that mediate the effect of CR have been heavily debated. Recently, it has become clear that dietary protein plays a key role in regulating both metabolic health and longevity, and that both the quantity and quality - the specific amino acid composition - of dietary protein mediates metabolic health. Here, we discuss recent findings in model organisms ranging from yeast to mice and humans regarding the influence of dietary protein as well as specific amino acids on metabolic health, and the physiological and molecular mechanisms which may mediate these effects. Read More

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A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases). Each section of this review concludes with key points from the relevant papers. The overall findings were that disturbed iron metabolism plays a major role in a large number of conditions associated with old age. Read More

Cardiovascular health deteriorates with age, and age is one of the strongest risk factors for cardiovascular complications including myocardial infarction, heart failure, cardiac arrhythmias, and death related to heart diseases. In this review, we show that expression of proinflammatory cytokines (PICs) increases throughout the human lifespan, and this increase is correlated with cardiovascular health, morbidity, and mortality. We argue that increased concentrations of circulating PICs are not only markers of chronic low-grade inflammation, but they also serve as an important pathophysiological link between CV health and ageing. Read More

Authors:

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Stem cells being pluripotent in nature can differentiate into a wide array of specific cells and asymmetrically divide to produce new ones but may undergo aging by themselves. Aging has both quantitative and qualitative effects on stem cells, and could eventually restrain them from replenishing into progenitor cells. Reactive oxygen species (ROS) accumulated in the aging cells could not only block the cell cycle but also affect autophagy by damaging the mitochondria. Read More

Linker histones are major players in chromatin organization and per se are essential players in genome homeostasis. As the fifth class of histone proteins the linker histones not only interact with DNA and core histones but also with other chromatin proteins. These interactions prove to be essential for the higher levels of chromatin organization like chromatin loops, transcription factories and chromosome territories. Read More

Authors:

INSIGNEO Institute for in silico Medicine, United Kingdom; Department of Oncology and Human Metabolism, University of Sheffield, United Kingdom.

Driven by the raising ethical concerns surrounding animal experimentation, there is a growing interest for non-animal methods, in vitro or in silico technologies that can be used to reduce, refine, and replace animal experimentation. In addition, animal experimentation is being critically revised in regard to its ability to predict clinical outcomes. In this manuscript we describe an initial exploration where a set of in vivo imaging based subject-specific technologies originally developed to predict the risk of femoral strength and hip fracture in osteoporotic patients, were adapted to assess the efficacy of bone drugs pre-clinically on mice. Read More

Ageing leads to substantial force production capacity reductions, which is an indicator of frailty and disability, and a mortality predictor in elders. Understanding the age-dependent neuromuscular mechanisms underlying force reductions can optimize healthcare professionals' exercise protocol choices for patients and allows researchers to investigate new interventions to mitigate these reductions. Our primary goal was to provide an updated review about the main neural and musculotendinous mechanisms underpinning age-related reductions in force capacity. Read More

Ageing is a multifactorial process that affects most, if not all, of the body's tissues and organs and can be defined as the accumulation of physical and psychological changes in a human being over time. The rate of ageing differs between individuals of the same chronological age, meaning that 'biological age' of a person may be different from 'chronological age'. Furthermore, ageing represents a very potent risk factor for diseases and disability in humans. Read More

Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to neurodegeneration, growth failure and premature aging. Most of the cases are due to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in several functions including DNA repair and transcription. Read More

Replicative capacity of normal human cells decreases as telomeric sequence is lost at each division. It is believed that when a subset of chromosomes reach a critically short length, an ATM-initiated and p53-mediated transcriptional response inhibits cell growth, promoting cell senescence. In addition to loss of telomeric sequence, senescence can be induced by other stresses including ionizing radiation, oxidative damage, chemical crosslinkers like the chemotherapeutic agent cisplatin, as well as overactivation of oncogenes and tumor suppressors. Read More

Deciphering the characteristics of dermal fibroblasts is critical to further understand skin ageing. We have conducted a genome-wide transcriptomic characterization of papillary (Fp) and reticular (Fr) fibroblasts extracted from human skin samples corresponding to younger and older adult ages. From this screen, biomarkers suitable for the assessment of chronological ageing were identified, and extrapolated to the context of photo-damaged skin. Read More

Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia. Electronic address:

Background: Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Read More

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Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt. Electronic address:

Cellular reprograming paves the way for creating functional patient-specific tissues to eliminate immune rejection responses by applying the same genetic profile. However, the epigenetic memory of a cell remains a challenge facing the current reprograming methods and does not allow transcription factors to bind properly. Because somatic cells can be reprogramed by transferring their nuclear contents into oocytes, introducing specific oocyte factors into differentiated cells is considered a promising approach for mimicking the reprograming process that occurs during fertilization. Read More

It is known that sarcopenia is a multifaceted phenomenon, which involves genetic, nutritional, hormonal and living habits aspects. Then, an integrated analysis, as a multivariate approach, could improve the comprehension about the determinants of sarcopenic state in old adults. The present study aimed to investigate the interaction among serum vitamin D, daily caloric and protein intake, lifestyle habits, ACE I/D gene polymorphism and sarcopenic state in community-dwelling old adults. Read More

Authors:

Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, the University of Southern California, Los Angeles, CA, 00089-0191, USA; Molecular & Computational Biology Program of the Department of Biological Sciences, Dornsife College of Letters, Arts, and sciences, the University of Southern California, Los Angeles, CA, 90089-0191, USA; Department of Biochemistry & Molecular Medicine, Keck School of Medicine of USC, the University of Southern California, Los Angeles, CA, USA. Electronic address:

Many consequences of ageing can be broadly attributed to the inability to maintain homeostasis. Multiple markers of ageing have been identified, including loss of protein homeostasis, increased inflammation, and declining metabolism. Although much effort has been focused on characterization of the ageing phenotype, much less is understood about the underlying causes of ageing. Read More

Authors:

Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece. Electronic address:

Intervertebral discs (IVDs) are the joints of the spine, mainly consisting of extracellular matrix (ECM) with a low number of cells embedded therein. Low cellularity stems from nutrient deprivation due to the lack of blood supply, as well as from the hypoxic and hyperosmotic conditions prevailing in the tissue. Intervertebral disc degeneration (IDD) has been firmly connected with low back pain, a major age-related disease, whereas degenerated discs have been characterized by increased proteolytic activity and accumulation of senescent cells. Read More

Authors:

The recognized role of neuroinflammation in the age-related deterioration of neuronal function highlights the importance of understanding the factors that control microglial activation. Microglia, as the immune cells of the brain, are the arbiters of the inflammatory profile in the brain. Normally they are maintained in a quiescent state by means of ligand-receptor interactions with neurons, within a prevailing anti-inflammatory microenvironment. Read More

Authors:

Department of Biology, University of Nevada, Reno, Nevada 89557, United States. Electronic address:

Circular RNAs (circRNAs) are a newly appreciated class of RNAs found across phyla that are generated most commonly from back-splicing of protein-coding exons. Recent profiling of circRNAs genome-wide has shown that hundreds of circRNAs dramatically increase in expression during aging in the brains of multiple organisms. No other class of transcripts has been found to show such a strong correlation with aging as circRNAs-could they be playing a role in the aging process? Here, we discuss the different methods used to profile circRNAs and discuss current limitations of these approaches. Read More

Progeroid syndrome is a group of disorders characterized by the early onset of diseases that are associated with aging. Best known examples are Werner syndrome, which is adult onset and results from disease-causing DNA sequence variants in the RecQ helicase gene WRN, and Hutchison-Gilford progeria syndrome, which is childhood-onset and results from unique, recurrent disease-causing DNA sequence variants of the gene LMNA that encodes nuclear intermediate filaments. Related single gene RecQ disorders are Bloom syndrome and Rothmund-Thomson syndrome. Read More

Authors:

Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. Read More

National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i. Read More

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